dbSNP rs3756505: CSNK1A1:c.857+67A>G (chr5-149506960-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001892.6(CSNK1A1):c.857+67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,177,532 control chromosomes in the GnomAD database, including 8,076 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1659 hom., cov: 32)

Exomes 𝑓: 0.11 ( 6417 hom. )

Consequence

CSNK1A1
NM_001892.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.109

Publications

5 publications found

Variant links:

Genes affected

CSNK1A1 (HGNC:2451): (casein kinase 1 alpha 1) Enables protein serine/threonine kinase activity. Involved in several processes, including negative regulation of canonical Wnt signaling pathway; peptidyl-serine phosphorylation; and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in centrosome; cytosol; and nuclear speck. Part of beta-catenin destruction complex. Colocalizes with keratin filament and mRNA cleavage and polyadenylation specificity factor complex. Biomarker of Alzheimer's disease and inclusion body myositis. [provided by Alliance of Genome Resources, Apr 2022]

CSNK1A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001892.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CSNK1A1	NM_001892.6	MANE Select	c.857+67A>G	intron	N/A	NP_001883.4
CSNK1A1	NM_001025105.3		c.941+67A>G	intron	N/A	NP_001020276.1
CSNK1A1	NM_001271741.2		c.857+67A>G	intron	N/A	NP_001258670.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CSNK1A1	ENST00000377843.8	TSL:1 MANE Select	c.857+67A>G	intron	N/A	ENSP00000367074.2
CSNK1A1	ENST00000261798.10	TSL:1	c.941+67A>G	intron	N/A	ENSP00000261798.6
CSNK1A1	ENST00000606719.6	TSL:2	c.950+67A>G	intron	N/A	ENSP00000475319.2

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20878

AN:

152114

Hom.:

1661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.0696

Gnomad FIN

AF:

0.0931

Gnomad MID

AF:

0.169

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.136

GnomAD4 exome

AF:

0.106

AC:

109141

AN:

1025300

Hom.:

6417

AF XY:

0.105

AC XY:

54167

AN XY:

517866

show subpopulations

African (AFR)

AF:

0.207

AC:

4953

AN:

23944

American (AMR)

AF:

0.122

AC:

3767

AN:

30806

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

3941

AN:

21516

East Asian (EAS)

AF:

0.183

AC:

6466

AN:

35430

South Asian (SAS)

AF:

0.0606

AC:

4148

AN:

68402

European-Finnish (FIN)

AF:

0.110

AC:

5487

AN:

50046

Middle Eastern (MID)

AF:

0.143

AC:

632

AN:

4428

European-Non Finnish (NFE)

AF:

0.0995

AC:

74155

AN:

745518

Other (OTH)

AF:

0.124

AC:

5592

AN:

45210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

4613

9226

13839

18452

23065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2504

5008

7512

10016

12520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.137

AC:

20916

AN:

152232

Hom.:

1659

Cov.:

AF XY:

0.136

AC XY:

10095

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.208

AC:

8638

AN:

41514

American (AMR)

AF:

0.129

AC:

1969

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

638

AN:

3472

East Asian (EAS)

AF:

0.179

AC:

925

AN:

5182

South Asian (SAS)

AF:

0.0705

AC:

340

AN:

4826

European-Finnish (FIN)

AF:

0.0931

AC:

988

AN:

10608

Middle Eastern (MID)

AF:

0.178

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.102

AC:

6961

AN:

68014

Other (OTH)

AF:

0.137

AC:

290

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

906

1812

2718

3624

4530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.117

Hom.:

1260

Bravo

AF:

0.146

Asia WGS

AF:

0.153

AC:

533

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.8

(source)

DANN

Benign

0.89

PhyloP100

0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over